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Therapeutic Electrical Stimulation of the Hypoglossal Nerve in Obstructive Sleep Apnea
Alan R. Schwartz, MD;
Marc L. Bennett, MD;
Philip L. Smith, MD;
Wilfried De Backer, MD;
Jan Hedner, MD;
An Boudewyns, MD;
Paul Van de Heyning, MD;
Hasse Ejnell, MD;
Walter Hochban, DDS, MD;
Lennart Knaack, MD;
Thomas Podszus, MD;
Thomas Penzel, PhD;
J. Hermann Peter, MD;
George S. Goding, MD;
Donald J. Erickson;
Roy Testerman, PhD;
Frans Ottenhoff, PhD;
David W. Eisele, MD
Arch Otolaryngol Head Neck Surg. 2001;127:1216-1223.
ABSTRACT
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Background Hypoglossal nerve stimulation has been demonstrated to relieve upper
airway obstruction acutely, but its effect on obstructive sleep apnea is not
known.
Objective To determine the response in obstructive sleep apnea to electrical stimulation
of the hypoglossal nerve.
Methods Eight patients with obstructive sleep apnea were implanted with a device
that stimulated the hypoglossal nerve unilaterally during inspiration. Sleep
and breathing patterns were examined at baseline before implantation and after
implantation at 1, 3, and 6 months and last follow-up.
Results Unilateral hypoglossal nerve stimulation decreased the severity of obstructive
sleep apnea throughout the entire study period. Specifically, stimulation
significantly reduced the mean apnea-hypopnea indices in non–rapid eye
movement (mean ± SD episodes per hour, 52.0 ± 20.4 for baseline
nights and 22.6 ± 12.1 for stimulation nights; P<.001) and rapid eye movement (48.2 ± 30.5 and 16.6 ±
17.1, respectively; P<.001) sleep and reduced
the severity of oxyhemoglobin desaturations. With improvement in sleep apnea,
a trend toward deeper stages of non–rapid eye movement sleep was observed.
Moreover, all patients tolerated long-term stimulation at night and did not
experience any adverse effects from stimulation. Even after completing the
study protocol, the 3 patients who remained free from stimulator malfunction
continued to use this device as primary treatment.
Conclusion The findings demonstrate the feasibility and therapeutic potential for
hypoglossal nerve stimulation in obstructive sleep apnea.
INTRODUCTION
OBSTRUCTIVE sleep apnea affects 2% to 4% of the adult population1 and is most commonly seen in middle-aged, overweight
men.2 It is caused by recurrent episodes of
upper airway obstruction during sleep that lead to periodic oxyhemoglobin
desaturations and arousals from sleep.3-4
Disturbances in sleep and oxygenation are believed to be responsible for the
major clinical manifestations of this disorder, which include daytime hypersomnolence,
arterial and pulmonary hypertension, and cardiopulmonary failure. The primary
goal of therapy is to avert or alleviate the clinical sequelae of this disorder
by relieving upper airway obstruction during sleep.5
Various methods have been used to relieve upper airway obstruction in apneic
patients, including nasal continuous positive airway pressure,6-9
weight reduction,10-11 positional
maneuvers,12 pharmacologic interventions,13-15 dental appliances,16-17 and upper airway reconstructive or
bypass surgery,18-22
all with varying degrees of success. Thus, no single treatment is certain
to provide complete relief of upper airway obstruction in all patients during
sleep.
The cause of upper airway obstruction is related to a decline in genioglossus
muscle activity during sleep and is not addressed by current therapy.3, 23 In previous studies, investigators
have demonstrated that short-term stimulation of the genioglossus can prevent
the tongue from prolapsing into the pharynx24-26
and relieve upper airway obstruction during sleep.26-28
Recently, a novel implantable hypoglossal nerve-stimulating device has been
developed to provide more prolonged genioglossal stimulation during sleep.
In the present clinical trial, we report responses in sleep and breathing
patterns to nightly stimulation for at least 6 months after implantation of
a hypoglossal nerve–stimulating device in 8 apneic patients.
PATIENTS AND METHODS
PATIENT SELECTION
Patients with sleep apnea were eligible if they had more than 10 apneas
per hour during non–rapid eye movement (NREM) sleep with predominantly
obstructive apneas on a screening overnight sleep study. Patients with concomitant
medical illness or neuromuscular or otolaryngologic disease were excluded.
A total of 8 men were enrolled; baseline anthropometric characteristics are
presented in Table 1. Three patients
(patients 1-3) were also selected from 1 center on the basis of nocturnal
pharyngeal manometric studies29 indicating
that they had predominantly retroglossal obstruction during sleep. The trial
was approved by the research ethics committees in all participating centers
and by competent authorities in the 4 centers' countries. Informed consent
was obtained for each patient.
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Table 1. Baseline Anthropometric and Sleep-Disordered Breathing Indices*
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INITIAL AND FOLLOW-UP EVALUATION
Each patient also underwent a screening history, a physical examination,
and an otolaryngologic examination. A standard overnight sleep study was performed
to characterize each patient's sleep and breathing patterns. In brief, standard
polysomnographic methods were used, which included monitoring of surface C3-A2
and C3-O1 electroencephalograms, submental electromyograms, and bilateral
electro-oculograms for staging of sleep and assessment of sleep-wake state.
Respiratory patterns were assessed by monitoring oxyhemoglobin saturation
with pulse oximetry, oronasal airflow by thermistor or pneumotachogram, and
thoracic and abdominal efforts by either piezoelectrodes or esophageal manometry.
The patient's electrocardiogram rhythm was also monitored continuously throughout
the night. Sleep studies were scored for sleep-wake state,30
presence and type of apneas or hypopneas (obstructive, mixed, or central),
changes in oxygen saturation, and arousals.31
Apnea and hypopnea were defined using previously published criteria.15
HYPOGLOSSAL NERVE–STIMULATING DEVICE
A stimulating device was designed to synchronize the delivery of stimulus
bursts with the patient's inspiration using the Inspire I stimulating system
(Medtronic Inc, Minneapolis, Minn). Unilateral stimulation was chosen in this
study for reasons of safety. The hypoglossal nerve–stimulation system
consisted of an implantable intrathoracic pressure sensor, a programmable
pulse-generating system, and a stimulating electrode. The pulse-generating
unit provided an excitation current for the sensor and monitored the sensor
signal to predict the onset of inspiration. Independent threshold and slope
parameters were used to detect the inspiratory and expiratory onset from the
intrathoracic pressure sensor waveform. These timing parameters were then
used to begin stimulation just prior to inspiratory onset and to continue
stimulation for the duration of the inspiration, provided that a previously
programmed expiratory refractory period had elapsed.
The pulse-generating unit delivered bursts of electrical impulses at
a set voltage amplitude, pulse width, and frequency. Stimulus parameters and
inspiratory sensing algorithms could be addressed using an external programming
unit. Impulses were delivered to the hypoglossal nerve via a lead and half-cuff
silicone-insulated, guarded, bipolar platinum electrode. A self-controlled
programming unit was provided for patients to initiate and terminate electrical
stimulation at will. Stimulation was set to begin after a preset delay of
0 to 30 minutes to allow patients to initiate sleep before the start of electrical
stimulation.
DEVICE IMPLANTATION PROCEDURE
The patients received general anesthesia, and no long-acting muscle
relaxants were used intraoperatively. Cefazolin was given perioperatively
and every 6 hours for the first 24 hours postoperatively. An upper neck incision
was made, and the main trunk of the hypoglossal nerve was identified by dissection
between the submandibular gland and the digastric tendon. The nerve was dissected
peripheral to a large inferior distal branch to the genioglossus muscle. A
peripheral branch was chosen for stimulation for reasons of safety and because
stimulating the peripheral or proximal hypoglossal nerve produced comparable
increases in airflow during sleep.26 A half-cuff
electrode was placed unilaterally around this branch and secured. The electrode
was connected to a pulse generator to confirm proper nerve branch placement
by observing tongue protrusion and contralateral deviation.28
A midline lower-neck Kocher incision was made to expose the manubrium, and
a pressure transducer was placed via a drill hole through the superior manubrium.
The implantable pulse generator was placed in an infraclavicular subcutaneous
pocket. The electrode lead and intrathoracic sensing lead were tunneled subcutaneously
and connected to the pulse-generating unit. Before the patient left the operating
room, the function of the entire implanted system was confirmed by observing
appropriate tongue movement with stimulation.
STIMULATION PROTOCOL AND FOLLOW-UP SLEEP STUDIES
After implantation, stimulation was not initiated for 4 weeks to avoid
disrupting hypoglossal nerve contact with the cuff electrode. Patients then
returned for sleep studies at 1, 3, and 6 months postoperatively. When possible,
for extended follow-up an additional sleep study night beyond the 6-month
time point was added for selected patients.
On the first stimulation night at 1 month postoperatively, tongue function
was assessed clinically. The motor recruitment and pain thresholds were then
determined during wakefulness with intermittent stimulation (91 microseconds;
pulse width, 33 Hz) at 0.1-V increments. After the onset of sleep, stimulation
was started at the motor recruitment threshold, and stimulus parameters were
increased to maximize tidal inspiratory airflow and to alleviate sleep-disordered
breathing episodes without electroencephalographic arousal.
On the second study night at 1 month postoperatively, optimal parameters
were used to stimulate the hypoglossal nerve for the entire night. Stimulation
was discontinued during awakenings of longer than 3 minutes and resumed once
patients reinitiated NREM sleep. During follow-up sleep studies at 3 and 6
months postoperatively, stimulus parameters were incremented as needed in
the initial 30 to 60 minutes of sleep to normalize breathing patterns and
maintained for the remainder of the night. During all sleep studies, patients
were allowed to sleep on their side or back in an unrestrained fashion.
DATA ANALYSIS
Sleep studies were scored for sleep and breathing patterns at baseline;
1, 3, and 6 months after implantation; and on the last available study night
with electrical stimulation. Two separate analyses were performed to account
for physiologic and device-related variability in response to stimulation.
In an intention-to-treat analysis, the entire night was evaluated with the
exception of the initial 30- to 60-minute period required for adjustment of
stimulus parameters. A further analysis of the polysomnographic recording
was performed to account for periods of stimulator malfunction and "off" time.
In this analysis, only prolonged periods of repeated, synchronous stimulation
were assessed for the purpose of characterizing sleep and breathing responses.
The longest uninterrupted NREM period in which no device malfunction was apparent
constituted a period of continuous stimulation.
Outcome variables included stimulus parameters and nocturnal sleep and
respiratory indices. Mixed-model generalized linear regression was used to
analyze responses (Minitab Inc, State College, Pa). A nested study design
was used to determine the response to electrical stimulation during treatment
vs baseline nights and to determine the response to electrical stimulation
across treatment nights. In this model, treatment and treatment night were
considered to be fixed factors, and the patient was considered to be a random
factor. When significant differences in the response were detected over time,
Bonferroni post hoc comparisons were performed to test for significant differences
between stimulation and baseline study nights. P<.05
was considered significant.
RESULTS
BASELINE CHARACTERISTICS
Patients were middle-aged, moderately overweight men with moderate to
severe obstructive sleep apnea during NREM and rapid eye movement (REM) sleep
(Table 1). Two patients (patients
2 and 5) had previously undergone uvulopalatopharyngoplasties. All patients
had been using nasal continuous positive airway pressure but discontinued
its use at the start of the trial.
STIMULUS PARAMETERS DURING INTERVENTION
Stimulus parameters are shown for the group over the trial period in Table 2. A significant increase in stimulus
voltage (P = .047) and frequency (P = .02) was required, particularly within the first 3 months of stimulation,
without any significant change in pulse width. Interval assessments of stimulation
were performed at 1 month (mean ± SE, 38 ± 15 days; n = 8),
3 months (103 ± 16 days; n = 7), 6 months (219 ± 31 days; n
= 8), and last follow up (345 ± 97 days; n = 6).
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Table 2. Stimulation Parameters*
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SLEEP RECORDINGS DURING HYPOGLOSSAL NERVE STIMULATION
In Figure 1, breathing patterns
are illustrated at the onset of hypoglossal nerve stimulation during a period
of continuous NREM sleep. Prior to the initiation of electrical stimulation
(Figure 1, left), 3 obstructive
hypopneas were evident (airflow and esophageal pressure tracings). These events
were associated with oxyhemoglobin desaturations (oxyhemoglobin saturation
waveform) and with arousals from sleep during which the submental electromyogram
amplitude and tidal airflow increased. After stimulation was started (intermittent
stimulus bursts in electromyogram recording, Figure 1, right), tidal airflow stabilized at higherlevels, and
arousals and oxyhemoglobin desaturations abated.
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Figure 1. Representative recording example
in 1 patient showing response in breathing pattern at the onset of hypoglossal
stimulation during a continuous period of non–rapid eye movement sleep.
Left, Before stimulation was started, 3 obstructive hypopneas were evident,
with periodic reductions in airflow terminated by microarousals from sleep
(rise in submental electromyogram [EMG] amplitude with resumption of tidal
airflow) and oxyhemoglobin desaturations. Right, Approximately 20 seconds
after the onset of the stimulus, tidal airflow stabilized, esophageal pressure
swings were reduced, and arousals and oxyhemoglobin desaturations were abolished.
EOG indicates electro-oculogram; EEG, C3-A2 electroencephalogram; PES, esophageal pressure; and SaO2, oxyhemoglobin saturation.
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SLEEP-DISORDERED BREATHING
Apnea-hypopnea indices in NREM and REM sleep are illustrated for baseline;
1, 3, and 6 months; and last follow-up night of stimulation (Figure 2). Hypoglossal nerve stimulation was associated with a significant
decrease in apnea-hypopnea indices from baseline across all treatment nights
(P<.001). In Table 3, sleep-disordered breathing indices are reported for baseline,
for entire-night studies, and for continuous-stimulation recording periods.
During entire-night recordings, the mean ± SD apnea-hypopnea index
decreased from a baseline value of 52.0 ± 20.4 to 22.6 ± 12.1
episodes per hour in NREM sleep (P<.001) and from
48.2 ± 30.5 to 16.6 ± 17.1 episodes per hour in REM sleep (P<.001). During periods of continuous stimulation, further,
nonsignificant (P>.99) decreases in apnea-hypopnea
indices to 15.5 ± 15.2 and 12.0 ± 17.6 episodes per hour were
observed for NREM and REM sleep, respectively. In addition, there were increases
from control night in the NREM baseline oxyhemoglobin saturation level (P = .03) and in the mean low oxygen saturation (P = .001) during disordered-breathing episodes for both the entire-night
and continuous-stimulation periods. In REM sleep, the baseline oxyhemoglobin
saturation level was unchanged from the control night (P = .71), whereas the mean low oxygen saturation level was increased
(P = .047) during both stimulation conditions compared
with baseline.
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Figure 2. Apnea-hypopnea indices during
non–rapid eye movement (NREM) and rapid eye movement (REM) sleep at
baseline; at 1, 3, and 6 months; and at last follow-up after implantation
of the hypoglossal nerve–stimulating device. A significant treatment
effect (P<.001) was observed without any significant
change in the response to stimulation over time. All values are mean ±
SE.
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Table 3. Sleep-Disordered Breathing Indices*
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In Figure 3, NREM apnea-hypopnea
indices are illustrated for baseline, entire-night, and continuous-stimulation
recording periods for each patient. Although no significant differences in
apnea-hypopnea indices were observed between the entire-night and continuous-stimulation
conditions, responses to the 2 stimulation conditions differed in selected
patients. For the entire-night recording, the apnea-hypopnea index decreased
markedly in 7 of 8 patients during NREM sleep and in each of the 6 patients
with significant apnea during REM sleep. During the continuous-stimulation
recording period, a further decrease in NREM apnea-hypopnea index was observed
in selected individuals (patients 1, 5, and 6) compared with the entire night.
These decreases could be attributed to periods of intermittent device malfunction
or asynchronous stimulation that were excluded from the analysis of continuous-stimulation
recordings in these patients.
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Figure 3. Non–rapid eye movement (NREM)
apnea-hypopnea indices for a night without stimulation (baseline) and for
entire-night and continuous periods with hypoglossal nerve stimulation. Patients'
values for the entire night are the mean of values at 1, 3, and 6 months and
last follow-up. A significant decrease in NREM sleep was observed between
the entire night and baseline night and between continuous stimulation and
baseline night (P<.001).
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SLEEP ARCHITECTURE
Sleep stage distribution is represented in Table 4 for the entire study period. Trends toward a reduced percentage
of stage I (transitional) NREM sleep (P = .16) and
an increased percentage of slow wave (deep) NREM sleep (P = .14) were observed during the stimulated nights compared with baseline,
but were not statistically significant. There were no significant differences
in sleep stage distribution among the treatment nights over the course of
the study.
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Table 4. Sleep Architecture*
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CLINICAL FOLLOW-UP
The implantable stimulating device operated well in all patients, was
well tolerated, relieved symptoms of sleep-disordered breathing, and replaced
nasal continuous positive airway pressure as the sole treatment modality in
these patients for at least 6 months. All patients reported continuous use
of the stimulator on a nightly basis. Patients' body mass index values (calculated
as weight in kilograms divided by the square of height in meters) remained
stable throughout the study period (mean ± SD, 29.3 ± 4.6 and
29.5 ± 4.4 at baseline and 6 months, respectively). At each follow-up
time point, the tongue was thoroughly examined, and no abnormalities in lingual
appearance or function (abnormal tongue deviation, atrophy, hypertrophy, fasciculations,
pain, numbness, inflammation, alterations in speech and swallowing) were detected
in any patient.
Subsequent device malfunction included pulse generator failure (patients
5 and 7), intermittent sensor shutdown (patient 6), transient asynchronous
stimulation due to sensor signal artifact (patients 4 and 8), and electrode
breakage (patients 3 and 8). At the time this article was written, 3 patients
were still using the stimulating system (patients 1, 2, and 4) as their sole
treatment.
COMMENT
The major finding of the present study was that nightly stimulation
in patients with moderate to severe obstructive sleep apnea markedly diminished
apnea severity without arousing patients from sleep. Specifically, the frequency
of obstructive apneic and hypopneic episodes decreased, and the severity of
oxyhemoglobin desaturations improved significantly. With improvement in sleep
apnea, a trend toward deeper stages of NREM sleep was observed. Moreover,
all patients tolerated long-term stimulation at night, and none experienced
any adverse effects from stimulation throughout the entire observation period.
The 3 patients remaining free from any stimulator malfunction continued to
use this device as a primary treatment for their apnea even after completing
the study protocol. Thus, these findings demonstrated that nightly unilateral
hypoglossal nerve stimulation is both feasible and of potential therapeutic
benefit for patients with obstructive sleep apnea.
Because of the temporary nature of the stimulator used, previous studies
on hypoglossal nerve stimulation have shown only short-term relief of upper
airway obstruction during sleep.26 With the
development of a fully implantable stimulating system, we were able to examine
the effect of nightly stimulation in the present study, and marked improvements
in the severity of obstructive sleep apnea were observed. We believe that
such improvements were primarily the result of activating the genioglossus
muscle, since the tongue protruded and deviated contralaterally during unilateral
stimulation.24-25 Indeed, selective
activation of the genioglossus was confirmed by noting such movement both
intraoperatively and postoperatively throughout the trial. Moreover, recruitment
of the genioglossus muscle during sleep led to prompt increases in inspiratory
airflow (Figure 1), a finding previously
attributed to a decrease in upper airway collapsibility27
or critical closing pressure. However, apnea was not eliminated entirely in
our patients, and intermittent inspiratory flow limitation (snoring) remained.
Although airway collapsibility was not measured, comparable levels of
stimulation have been associated previously with a decrease in critical pressure
of approximately 5 cm of water32 and persistent
airway obstruction.26, 28 On the
basis of these findings, it is likely that the greatest improvement in apnea
occurred in patients with the least collapsible airways (lowest critical pressure
at baseline).5, 33-34
Alternatively, greater reductions in both the critical pressure and apnea
severity might have been achieved with an increase in stimulus intensity or
with bilateral stimulation in those patients with suboptimal responses. Given
the apparent safety of unilateral stimulation in our patients, it might now
be possible to stabilize the airway mechanically with more uniform bilateral
hypoglossal nerve stimulation.
Broad selection criteria were adopted for this initial series and probably
contributed to the variability in the response to stimulation. No single factor
could be discerned that predicted an optimal outcome. Nevertheless, retroglossal
obstruction appeared advantageous, since the most marked improvements in apnea
occurred in patients 1, 2, and 3, in whom retroglossal obstruction had been
demonstrated previously in a nocturnal pharyngeal manometric study.29 Another patient (patient 5), who also had an excellent
response to stimulation, was suspected of having retroglossal obstruction
because he had not responded to uvulopalatopharyngoplasty.35
Additional variability in the response to hypoglossal nerve stimulation may
also have been caused by differences in anatomy or different patterns in pharyngeal
and cervical muscle activity during sleep.36
Additional studies of airway anatomy or physiology, however, have not been
performed; thus, the factors required for optimal responses are unknown.
One general concern is that microarousals could have accounted for improvements
in airway patency during stimulation.3-4,28, 37-39
We do not believe this to have been the case for the following reasons: First,
cortical arousal was not apparent in electroencephalographic recordings spanning
many nights.31 Second, we and others have observed
that cortical arousal is usually associated with sustained improvements in
tidal airflow beyond the stimulus burst28, 37-38
(Figure 1). Third, if frequent arousals
had occurred, disturbances in sleep architecture (consisting of an increase
in stage I sleep and decreases in deeper stages of NREM [stages II-IV] and
REM sleep) would have been expected. Rather, we found trends toward deeper
stages of NREM sleep during stimulation nights (Table 4), and thus we believe that improvements in apnea were related
to selective genioglossus muscle recruitment instead of arousal.
Several technical issues with the current device limited its immediate
application. First, poor synchronization in selected patients (patients 1
and 6) and device malfunction (patient 5) diminished the sustained improvement
in apnea. Nevertheless, when the stimulation was well synchronized with inspiration,
improvement in apnea was consistently observed. In one patient (patient 7),
despite good synchronization, the apnea-hypopnea index did not fall, although
stimulation partially restored this patient's airway patency as manifested
by increased hypopneas (partial airflow obstruction) instead of apneas (complete
airflow obstruction). Second, small but consistent increases in stimulus parameters
were also required early in the protocol to maintain responses in apnea-hypopnea
indices.40 However, it should be noted that
little further increase in stimulus intensity was required beyond 3 months,
suggesting that the electrode-nerve interface stabilized thereafter. Finally,
electrode breakage and sensor malfunction (5 of 8 patients) compromised long-term
stimulation beyond 6 months. Nevertheless, responses in the apnea-hypopnea
index during entire nights and for continuous periods of stimulation suggest
that the therapeutic potential for hypoglossal nerve stimulation will be fully
realized once these technical issues are solved and stimulus parameters are
optimized.
In summary, the present findings demonstrate the potential for hypoglossal
nerve stimulation as a novel form of therapy for obstructive sleep apnea.
Further studies will be required to optimize patient selection criteria based
on baseline differences in upper airway function or the site of pharyngeal
obstruction. It should also be noted that improvements in sleep-disordered
breathing might be further augmented with bilateral hypoglossal nerve stimulation
and/or stimulation of other upper airway and cervical muscles. Finally, the
effect of nightly stimulation on measures of daytime performance, sleepiness,
and cardiovascular function will have to be assessed before the role of hypoglossal
nerve stimulation as a therapeutic option for treating obstructive sleep apnea
can be established.
AUTHOR INFORMATION
Accepted for publication March 3, 2001.
The research was supported by a grant from Medtronic Inc; by grants
HL37379 and HL50381 from the National Institutes of Health, Bethesda, Md;
and by a grant from the Swedish Heart and Lung Foundation, Goteborg.
Corresponding author and reprints: Alan R. Schwartz, MD, 5501 Hopkins
Bayview Cir, Baltimore, MD 21224 (e-mail: Schwartz{at}jhmi.edu).
From the Johns Hopkins Sleep Disorders Center and Department of Otolaryngology–Head
and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore,
Md (Drs Schwartz, Bennett, Smith, and Eisele); University Hospital Antwerp
Sleep Center, Antwerp, Belgium (Drs De Backer, Boudewyns, and Van de Heyning);
Departments of Clinical Pharmacology (Dr Hedner) and Otolaryngology–Head
and Neck Surgery (Dr Ejnell), Sahlgrenska University Hospital, Goteborg, Sweden;
Sleep Medicine Laboratory, Pulmonary Division and Department of Internal Medicine,
Hospital of the Phillips University of Marburg, Marburg, Germany (Drs Hochban,
Knaack, Podszus, Penzel, and Peter); Department of Otolaryngology–Head
and Neck Surgery, Hennepin County Medical Center, University of Minnesota,
Minneapolis (Dr Goding); and Medtronic Upper Airway, Minneapolis (Mr Erickson
and Dr Testerman), and Maastricht, the Netherlands (Dr Ottenhoff). Drs Schwartz,
Smith, Van de Heyning, De Backer, and Eisele have served as medical advisors
to Medtronic Inc (Minneapolis, Minn), and Dr Goding is currently a medical
advisor to Medtronic Inc. None of the investigators has any financial interest
in Medtronic Inc or any of its products.
REFERENCES
| |
1. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328:1230-1235.
FREE FULL TEXT
2. Redline S, Kump K, Tishler PV, Browner I, Ferrette V. Gender differences in sleep-disordered breathing in a community-based
sample. Am J Respir Crit Care Med. 1994;149(3 pt 1):722-726.
3. Remmers JE, deGroot WJ, Sauerland EK, Anch AM. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol. 1978;44:931-938.
FREE FULL TEXT
4. Gastaut H, Tassinari CA, Duron B. Polygraphic study of diurnal and nocturnal (hypnic and respiratory)
episodal manifestations of Pickwick syndrome [in French]. Rev Neurol (Paris). 1965;112:568-579.
PUBMED
5. Gold AR, Schwartz AR. The pharyngeal critical pressure: the whys and hows of using nasal
continuous positive airway pressure diagnostically. Chest. 1996;110:1077-1088.
FREE FULL TEXT
6. Sullivan CE, Issa FG, Berthon-Jones M, Eves L. Reversal of obstructive sleep apnoea by continuous positive airway
pressure applied through the nares. Lancet. 1981;1:862-865.
ISI
| PUBMED
7. Reeves-Hoche MK, Meck R, Zwillich CW. Nasal CPAP: an objective evaluation of patient compliance. Am J Respir Crit Care Med. 1994;149:149-154.
ABSTRACT
8. Kribbs NB, Pack AI, Kline LR, et al. Objective measurement of patterns of nasal CPAP use by patients with
obstructive sleep apnea. Am Rev Respir Dis. 1993;147:887-895.
ISI
| PUBMED
9. Weaver TE, Kribbs NB, Pack AI, et al. Night-to-night variability in CPAP use over the first three months
of treatment. Sleep. 1997;20:278-283.
ISI
| PUBMED
10. Smith PL, Gold AR, Meyers DA, Haponik EF, Bleecker ER. Weight loss in mildly to moderately obese patients with obstructive
sleep apnea. Ann Intern Med. 1985;103(6 pt 1):850-855.
11. Strobel RJ, Rosen RC. Obesity and weight loss in obstructive sleep apnea: a critical review. Sleep. 1996;19:104-115.
ISI
| PUBMED
12. Cartwright RD. Effect of sleep position on sleep apnea severity. Sleep. 1984;7:110-114.
ISI
| PUBMED
13. Brownell LG, West P, Sweatman P, Acres JC, Kryger MH. Protriptyline in obstructive sleep apnea: a double-blind trial. N Engl J Med. 1982;307:1037-1042.
ABSTRACT
14. Hanzel DA, Proia NG, Hudgel DW. Response of obstructive sleep apnea to fluoxetine and protriptyline. Chest. 1991;100:416-421.
FREE FULL TEXT
15. Smith PL, Haponik EF, Allen RP, Bleecker ER. The effects of protriptyline in sleep-disordered breathing. Am Rev Respir Dis. 1983;127:8-13.
ISI
| PUBMED
16. American Sleep Disorders Association. Practice parameters for the treatment of snoring and obstructive sleep
apnea with oral appliances. Sleep. 1995;18:511-513.
ISI
| PUBMED
17. Schmidt-Nowara W, Lowe A, Wiegand L, Cartwright R, Perez-Guerra F, Menn S. Oral appliances for the treatment of snoring and obstructive sleep
apnea: a review. Sleep. 1995;18:501-510.
ISI
| PUBMED
18. Conradt R, Hochban W, Brandenburg U, Heitmann J, Peter JH. Long-term follow-up after surgical treatment of obstructive sleep apnoea
by maxillomandibular advancement. Eur Respir J. 1997;10:123-128.
ABSTRACT
19. Mickelson SA. Upper airway bypass surgery for obstructive sleep apnea syndrome [review]. Otolaryngol Clin North Am. 1998;31:1013-1023.
FULL TEXT
|
ISI
| PUBMED
20. Fujita S, Conway W, Zorick F, Roth T. Surgical correction of anatomic abnormalities in obstructive sleep
apnea syndrome: uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg. 1981;89:923-934.
ISI
| PUBMED
21. Shepard JW Jr, Olsen KD. Uvulopalatopharyngoplasty for treatment of obstructive sleep apnea
[review]. Mayo Clin Proc. 1990;65:1260-1267.
ISI
| PUBMED
22. Riley RW, Powell NB, Guilleminault C. Obstructive sleep apnea syndrome: a review of 306 consecutively treated
surgical patients. Otolaryngol Head Neck Surg. 1993;108:117-125.
ISI
| PUBMED
23. Safar P, Escarraga LS, Chang F. Upper airway obstruction in the unconscious patient. J Appl Physiol. 1959;14:760-764.
FREE FULL TEXT
24. Abd-el-Malek S. A contribution to the study of the movements of the tongue in animals,
with special reference to the cat. J Anat. 1938;73:15-30.
ISI
| PUBMED
25. Bennett GA, Hutchinson RC. Experimental studies on the movements of the mammalian tongue. Anat Rec. 1946;94:59-72.
26. Eisele DW, Smith PL, Alam DS, Schwartz AR. Direct hypoglossal nerve stimulation in obstructive sleep apnea. Arch Otolaryngol Head Neck Surg. 1997;123:57-61.
FREE FULL TEXT
27. Schwartz AR, Thut DC, Russ B, et al. Effect of electrical stimulation of the hypoglossal nerve on airflow
mechanics in the isolated upper airway. Am Rev Respir Dis. 1993;147:1144-1150.
ISI
| PUBMED
28. Schwartz AR, Eisele DW, Hari A, Testerman R, Erickson D, Smith PL. Electrical stimulation of the lingual musculature in obstructive sleep
apnea. J Appl Physiol. 1996;81:643-652.
FREE FULL TEXT
29. Boudewyns A, Van de Heyning PH, De Backer WA. Site of upper airway obstruction in obstructive apnoea and influence
of sleep stage. Eur Respir J. 1997;10:2566-2572.
ABSTRACT
30. Rechtschaffen A, Kales A. A Manual of Standardized Terminology, Techniques
and Scoring Systems for Sleep Stages of Human Subjects. Washington, DC: National Institutes of Health; 1968. Publication
NIH 204.
31. Atlas Task Force. EEG arousals: scoring rules and examples: a preliminary report from
the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association. Sleep. 1992;15:174-184.
ISI
32. O'Hearn DJ, Schneider H, LeBlanc K, Schubert, O'Donnell CP, Smith PL, Schwartz AR. Effect of unilateral hypoglossal stimulation on upper airway function
[abstract]. Am J Respir Crit Care Med. 1998;157:A284.
33. Schwartz AR, Gold AR, Schubert N, et al. Effect of weight loss on upper airway collapsibility in obstructive
sleep apnea. Am Rev Respir Dis. 1991;144(3, pt 1):494-498.
34. Schwartz AR, Schubert N, Rothman W, et al. Effect of uvulopalatopharyngoplasty on upper airway collapsibility
in obstructive sleep apnea. Am Rev Respir Dis. 1992;145:527-532.
ISI
| PUBMED
35. Launois SH, Feroah TR, Campbell WN, et al. Site of pharyngeal narrowing predicts outcome of surgery for obstructive
sleep apnea. Am Rev Respir Dis. 1993;147:182-189.
ISI
| PUBMED
36. Fuller DD, Williams JS, Janssen PL, Fregosi RF. Effect of co-activation of tongue protrudor and retractor muscles on
tongue movements and pharyngeal airflow mechanics in the rat. J Physiol (Lond). 1999;519:601-613.
FREE FULL TEXT
37. Decker MJ, Haaga J, Arnold JL, Atzberger D, Strohl KP. Functional electrical stimulation and respiration during sleep. J Appl Physiol. 1993;75:1053-1061.
FREE FULL TEXT
38. Edmonds LC, Daniels BK, Stanson AW, Sheedy III PF, Shepard JW Jr. The effects of transcutaneous electrical stimulation during wakefulness
and sleep in patients with obstructive sleep apnea. Am Rev Respir Dis. 1992;146:1030-1036.
ISI
| PUBMED
39. Guilleminault C, Powell N, Bowman B, Stoohs R. The effect of electrical stimulation on obstructive sleep apnea syndrome. Chest. 1995;107:67-73.
FREE FULL TEXT
40. Goding GS Jr, Eisele DW, Testerman R, Smith PL, Roertgen K, Schwartz AR. Relief of upper airway obstruction with hypoglossal nerve stimulation
in the canine. Laryngoscope. 1998;108:162-169.
FULL TEXT
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ISI
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